Study of Anti-HB-EGF Antibody KHK2866 in Subjects With Advanced Solid Tumors and Ovarian Cancer

This study has been terminated.
(The study was stopped due to the inability to determine an acceptable dose with the potential for further study)
Sponsor:
Information provided by (Responsible Party):
Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01279291
First received: January 11, 2011
Last updated: March 5, 2013
Last verified: March 2013
  Purpose

This is a two-part, Phase 1, open-label, multicenter, dose escalation study of KHK2866 as monotherapy in patients with advanced solid tumors, and in combination with chemotherapy in subjects platinum-sensitive and platinum-resistant ovarian cancer.


Condition Intervention Phase
Neoplasms
Ovarian Neoplasms
Fallopian Tube Neoplasms
Primary Peritoneal Neoplasm
Biological: KHK2866
Drug: Gemcitabine and Carboplatin
Drug: paclitaxel
Drug: pegylated liposomal doxorubicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Anti-HB-EGF Monoclonal Antibody KHK2866 as Monotherapy in Subjects With Advanced Solid Tumors and in Combination With Chemotherapy in Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Kyowa Hakko Kirin Pharma, Inc.:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: at least 60 days, and up to 6 months ] [ Designated as safety issue: Yes ]
    The safety of KHK2866 will be determined by reported adverse events (AEs), changes in physical examinations, vital sign measurements, electrocardiograms (ECGs), clinical laboratory evaluations, and treatment discontinuation due to toxicity.


Secondary Outcome Measures:
  • To determine the Cmax, Tmax, AUC and half life of KHK2866 when administered i.v. as monotherapy [ Time Frame: at least 28 days and up to 6 months ] [ Designated as safety issue: No ]
    Participants will have serial blood samples taken to determine the PK profile of the study drug.

  • To evaluate the changes in serum HB-EGf in participants administered KHK2866 [ Time Frame: at least 60 days, and up to 6 months ] [ Designated as safety issue: No ]
    Participants will have serial blood samples taken to develop the PD profile.

  • To screen for the development of antibodies against KHK2866 (immunogenicity). [ Time Frame: at least 60 days and up to 6 months ] [ Designated as safety issue: Yes ]
    Participants will have serial blood samples to check for the development of anti-KHK2866 antibodies.

  • To describe any anti-tumor activity observed when KHK2866 is administered i.v. as monotherapy, or in combination with chemotherapy. [ Time Frame: at least 60 days and up to 6 months ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: January 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: KHK2866 as monotherapy
Groups of subjects will receive a weekly infusions of KHK2866 as treatment for advanced cancer. If there no severe side effects, the dose will be increased for future subjects. A total of four groups are anticipated. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.
Biological: KHK2866
Potentially therapeutic monoclonal antibody for the treatment of advanced cancer and ovarian cancer.
Experimental: KHK2866, gemcitabine+carboplatin

Open to subjects with ovarian, fallopian tube, or primary peritoneal cancer only.

One group of subjects will receive one dose below the maximum tolerated dose of KHK2866 identified in Phase 1a along with gemcitabine and carboplatin. The dose of KHK2866 will be increased to the MTD for the next group if no severe side effects are noted. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866
Potentially therapeutic monoclonal antibody for the treatment of advanced cancer and ovarian cancer.
Drug: Gemcitabine and Carboplatin
Combination chemotherapy with KHK2866 to treat advanced platinum-sensitive ovarian cancer. Gemcitabine dose 1000 mg/m2, Carboplatin dose AUC=4
Other Name: Gemzar, Paraplatin
Experimental: KHK2866, weekly paclitaxel

Open to subjects with ovarian, fallopian tube, or primary peritoneal cancer only.

One group of subjects will receive one dose below the maximum tolerated dose of KHK2866 identified in Phase 1a along with weekly paclitaxel (80 mg/m2). The dose of KHK2866 will be increased to the MTD for the next group if no severe side effects are noted. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866
Potentially therapeutic monoclonal antibody for the treatment of advanced cancer and ovarian cancer.
Drug: paclitaxel
Combination chemotherapy with KHK2866 to treat advanced platinum-resistant ovarian cancer. Paclitaxel will be administered weekly at a dose of 80 mg/m2.
Other Name: Taxol
Experimental: KHK2866, pegylated liposomal doxorubicin

Open to subjects with ovarian, fallopian tube, or primary peritoneal cancer only.

One group of subjects will receive one dose below the maximum tolerated dose of KHK2866 identified in Phase 1a along with monthly PLD (40 mg/m2). The dose of KHK2866 will be increased to the MTD for the next group if no severe side effects are noted. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866
Potentially therapeutic monoclonal antibody for the treatment of advanced cancer and ovarian cancer.
Drug: pegylated liposomal doxorubicin
Combination chemotherapy with KHK2866 to treat advanced platinum-resistant ovarian cancer. PLD will be administered weekly at a dose of 40 mg/m2.
Other Name: Doxil

Detailed Description:

During Phase 1a, groups of eligible patients with advanced solid tumors will receive KHK2866 as monotherapy in escalating doses. The Phase 1b portion will enroll patients with ovarian cancer who will receive KHK2866 in combination with one of three chemotherapy regimens (Arms): gemcitabine+carboplatin (platinum-sensitive, weekly paclitaxel (platinum-resistant), or pegylated liposomal doxorubicin (platinum-resistant). Escalating doses of the combination of KHK2866 and the chemotherapy regimen will given to two groups of subjects per Arm. The goal of the study is to learn about the side effects of KHK2866 alone or given in combination with chemotherapy. All subjects will receive study therapy for up to 6 cycles (up to 12 cycles for subjects assigned to PLD [Arm 3 of Phase 1b]), or until disease progression, the development of severe side effects, noncompliance or withdrawal of consent by the subject, or other removal criteria whichever comes first.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented, measurable or non-measurable, advanced primary or recurrent solid tumor (Phase 1a only) which is unresponsive to standard therapy or for which there is no standard therapy available.
  • Histologically or cytologically documented ovarian, primary peritoneal, or fallopian tube cancer.
  • The subject has objective radiographic disease progression and either unmeasurable or measurable disease during or following the last treatment regimen, or serum cancer antigen-125 (CA-125) greater than 2X the upper limit of normal ([ULN] >70 U/mL
  • Life expectancy >3 months.
  • Performance status < 3 at study entry.
  • Age > 18 years.
  • Normal left ventricular ejection fraction.
  • Recovered from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other therapies for cancer
  • Preserved hepatic, renal, and hematopoetic organ function.
  • Male and female subjects must use medically accepted contraception.

Exclusion Criteria:

  • Ovarian malignancy of low malignant potential.
  • Received anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks prior to the first dose of KHK2866 (6 weeks for nitrosourea or mitomycin chemotherapy).
  • received Mabs or had major surgery within 4 weeks of the first dose of KHK2866.
  • Requires administration of a prohibited medication or treatment including: prophylactic use of erythroid and/or granulocyte colony stimulating factors; concurrent anti-cancer treatment; biologic response modifiers for any condition
  • Brain metastases, leptomeningeal or primary brain neoplasm, even if treated.
  • Previously untreated or uncontrolled epidural metastasis
  • Cerebrovascular accident, Transient ischemic attack; symptomatic head trauma, or seizures or any kind within 6 months
  • Dementia, or other disorders of mentation or difficulty speaking or difficulty with comprehension.
  • Suspected impending bowel obstruction
  • The subject is pregnant,or is lactating.
  • Significant uncontrolled intercurrent illness
  • Known HIV infection or AIDS-related illness.
  • Known active hepatitis B or C or other active liver disease.
  • Psychiatric illness, disability or social situation that would compromise the subject's safety, ability to provide consent, or limit his/her compliance with study requirements.
  • Experienced a unmanageable hypersensitivity reactions to Mabs or other therapeutic proteins.
  • History of second primary cancer, with the exception of: a) curatively resected non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 2 years.
  • Additional exclusion criteria for subjects proposed for enrollment into the Phase 1b portion:

    • History of hypersensitivity or infusion reaction to any of the proposed chemotherapy arm's agents that could not be controlled with pre-medication and/or infusion rate adjustment;
    • Prior treatment with KHK2866;
    • History of Grade ≥ 3 non-hematologic or Grade 4 hematologic toxicity attributable to any of the proposed chemotherapy arm's agents
    • For subjects proposed to receive treatment with KHK2866 plus PLD: prior total cumulative exposure to doxorubicin must be ≤ 240 mg/m2.
  • Subjects with a known history of interstitial lung disease or pulmonary fibrosis. Subjects must have pulse oximetry >88% on room air at rest, and a DLco of >49% if there is no evidence of lung metastasis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01279291

Locations
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Cedar Sinai-Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, United States, 90048
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Texas
Oncology Consultants
Houston, Texas, United States, 77030
Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Kyowa Hakko Kirin Pharma, Inc.
Investigators
Study Director: Bruce A Silver, M.D. Kyowa Hakko Kirin Pharma, Inc.
  More Information

No publications provided

Responsible Party: Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01279291     History of Changes
Other Study ID Numbers: 2866-US-001
Study First Received: January 11, 2011
Last Updated: March 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Kyowa Hakko Kirin Pharma, Inc.:
advanced solid tumor
Ovarian cancer
Primary peritoneal cancer
Fallopian tube cancer

Additional relevant MeSH terms:
Neoplasms
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Antibodies
Antibodies, Monoclonal
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Carboplatin
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 01, 2014